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Enhanced regeneration of rabbit mandibular defects through a combined treatment of electrical stimulation and rhBMP-2 application |
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| Authors: | Junghoon Kim Hoon Joo Yang Tae Hyung Cho Sung Eun Lee Yong Doo Park Hyun Man Kim In Sook Kim Young-kwon Seo Soon Jung Hwang Sung June Kim |
| Affiliation: | 1. Department of Electrical and Computer Engineering, Seoul National University, Seoul, South Korea 2. Dental Research Institute, Brain Korea 21 2nd Program for Craniomaxillofacial Life Science, Seoul National University, Seoul, South Korea 3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Brain Korea 21 2nd Program for Craniomaxillofacial Life Science, Seoul National University, Seoul, South Korea 4. Biomedical Engineering, Brain Korea 21, 2nd Project for Biomedical Science, Korea University Medical College, Korea University, Seoul, South Korea 5. Department of Biomedical Engineering, Dental Research Institute, Korea University Medical College, School of Dentistry, Korea University, Seoul National University, Seoul, South Korea 6. Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, Dental Research Institute and School of Dentistry, Seoul National University, Seoul, South Korea 7. Laboratory for Biomaterials and Tissue Engineering Research, Department of Medical Biotechnology, Dongguk University, Seoul, South Korea |
| Abstract: | We evaluated the new bone regeneration of a rabbit mandibular defect using hBMSCs under electrical stimulation combined with rhBMP-2 in this study. An inner scaffold prepared by setting a collagen sponge with hBMSCs and hydrogel was placed into a polycaprolactone (PCL) outer box, and an electrical stimulation device was installed between the inner scaffold and the outer box. There were three experimental groups depending on electrical stimulation and application of rhBMP-2. The experimental group was divided into the following three groups. Group 1, in which rhBMP-2 (5 μg/defect) was added to hydrogel and electrical stimulation was not applied; Group 2, in which rhBMP-2 (5 μg/defect) was added as in Group 1 and electrical stimulation was applied; and Group 3, in which electrical stimulation was applied and rhBMP-2 (5 μg/defect) was injected directly into defect site. The delivered electrical stimulation was charge-balanced bi-phasic electric current pulses, and electrical stimulation was conducted for 7 days. The stimulation parameters of the bi-phasic electrical current set at an amplitude of 20 μA, a duration of 100 μs and a frequency of 100 Hz. Four weeks after surgery, new bone formation in each group was evaluated using radiography, histology, and micro-computed tomography (μCT). Groups 2 and 3 exhibited a significant increase in new bone formation compared to Group 1, while Group 3 showed the highest level of new bone regeneration. In a comparison between two groups, Group 2 showed a higher bone volume (BV) by 260 % (p < 0.01) compared with Group 1, and Group 3 showed a higher BV by 442 % (p < 0.01) compared with Group 1. The trend of the bone surface density (ratio of new bone to the real defect volume, BS/TV), trabecular number, and connectivity was identical to that of the BV. The total bone mineral density (BMD) of Groups 2 and 3 showed values higher by the ratios of 103 % (p < 0.01) and 107.5 % (p < 0.01) compared with Group 1, respectively. Part BMD for Groups 2 and 3 showed higher values by the ratios of 104.9 % (p < 0.01) and 122.4 % (p < 0.01) compared with Group 1, respectively. These results suggest that the combined treatment of electrical stimulation, hBMSCs, a collagen sponge, hydrogel, and rhBMP-2 was effective for bone regeneration of large-size mandibular defects. The application of rhBMP-2 with an injection following electrical stimulation demonstrated better efficiency as regards bone regeneration. |
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